1. The Invention
This invention relates to a novel process for the preparation of (dl)-13-substituted sulfinyl-prostaglandin-like [(dl)-2.alpha.-substituted-3.beta.-(1.alpha.-substituted sulfinyl-trans-2-alkenyl)-1-oxygenated cyclopentane and (dl)-2.alpha.-substituted-3.beta.-(1.alpha.-substituted sulfinyl-trans-2-alkenyl)-4.alpha.-hydroxy-1-oxygenated cyclopentane] compounds.
More particularly, it relates to a novel process for the preparation of the prostaglandin-like compounds of Formulas (A) and (B) above (whose nomenclature is discussed more fully below) from known prostaglandin and prostaglandin-like compounds.
2. The Prior Art
Prostaglandins have classically been described as chemically related 20-carbon chain hydroxy fatty acids having the basic skeleton of prostanoic acid: ##SPC4##
The prostaglandins having an hydroxyl group at the C-11 position and a keto group at the C-9 position are known as the PGE series, those having an hydroxyl group in place of the keto group are known as the PGF series and are further designated by .alpha. or .beta. suffix to indicate the configuration of the hydroxyl group at said position. The natural compounds are the .alpha.-hydroxy substituted compounds. They may contain different degrees of unsaturation in the molecule, particularly at C-5, C-13 and C-17, the unsaturation is also indicated by a suffix. Thus, for example, PGE.sub.1 refers to a prostanoic acid having a trans olefin bond at the 13-position. For a review on prostaglandins and the definition of primary prostaglandins, see, for example, S. Bergstrom, Recent Progress in Hormone Research 22, pp. 153-175 (1966) and Science 157, page 382 (1967) by the same author.
Prostaglandins are widely distributed in mammalian tissues and have been isolated from natural sources in very small amounts. In addition a number of the natural occurring prostaglandins have been prepared by chemical synthesis; note, for example, J. Am. Chem. Soc. 91, 5675 (1969), J. Am. Chem. Soc. 92, 2586 (1970) and J. Am. Chem. Soc. 93, 1489-1493 (1971) and references cited therein, W.P. Schneider et al., J. Am. Chem. Soc. 90, 5895 (1968) U. Axen et al., Chem. Commun., 303 (1969), and W.P. Schneider, Chem. Commun., 304 (1969).
Because of the remarkable range of biological and pharmacological properties exhibited by this family of compounds, a great deal of interest has focused upon such compounds and accordingly we have discovered a novel process for the preparation of (dl)-13-sulfinyl-prostaglandin-like [(dl)-2.alpha.-substituted-3.beta.-(1.alpha.-substituted sulfinyl-trans-2-alkenyl)-1-oxygenated cyclopentane and (dl)-2.alpha.-substituted-3.beta.-(1.alpha.-substituted sulfinyl-trans-2-alkenyl)-4.alpha.-hydroxy-1-oxygenated cyclopentane] compounds.